Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens

• Published in: Annals of oncology Vol. 20; no. 6; pp. 1026 - 1031
• Main Authors: Blackwell, K. L., Pegram, M. D., Tan-Chiu, E., Schwartzberg, L. S., Arbushites, M. C., Maltzman, J. D., Forster, J. K., Rubin, S. D., Stein, S. H., Burstein, H. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2009; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - secondary; Disease Progression; EGFR; ErbB1; ErbB2; Female; Gynecology. Andrology. Obstetrics; Humans; Lapatinib; Mammary gland diseases; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Quinazolines - therapeutic use; Receptor, ErbB-2 - biosynthesis; Trastuzumab; Treatment Failure; Treatment Outcome; Tumors; tyrosine kinase inhibitor; lapatinib; tyrosine kinase inhibitor; ErbB2; ErbB1; EGFR; Antineoplastic agent; Breast disease; erbB2 Gene; Gene overexpression; Monoclonal antibody; Metastasis; Epidermal growth factor receptor; Advanced stage; Lapatinib; Protein-tyrosine kinase; Protooncogene; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Breast cancer; Malignant tumor; Human Epidermal growth factor Receptor 2; First line treatment; Mammary gland diseases; C-Onc gene; Therapeutic protocol; Trastuzumab; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdn759

Background: This phase II study evaluated the efficacy and safety of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer that progressed during prior trastuzumab therapy. Patients and methods: Women with stage IIIB/IV HER2-overexpressing breast cancer were treated with single-agent lapatinib 1250 or 1500 mg once daily after protocol amendment. Tumor response according to RECIST was assessed every 8 weeks. HER2 expression was assessed in tumor tissue by immunohistochemistry and FISH. Results: Seventy-eight patients were enrolled in the study. Investigator and independent review response rates [complete response (CR) or partial response (PR)] were 7.7% and 5.1%, and clinical benefit rates (CR, PR, or stable disease for ≥24 weeks) were 14.1% and 9.0%, respectively. Median time to progression was 15.3 weeks by independent review, and median overall survival was 79 weeks. The most common treatment-related adverse events were rash (47%), diarrhea (46%), nausea (31%), and fatigue (18%). Conclusions: Single-agent lapatinib has clinical activity with manageable toxic effects in HER2-overexpressing breast cancer that progressed on trastuzumab-containing therapy. Studies of lapatinib-based combination regimens with chemotherapy and other targeted therapies in metastatic and earlier stages of breast cancer are warranted.